tbuckley/cabot-search huggingface dataset:
Programming an Enhanced Uptake and the Intracellular Fate of Magnetic Microbeads
Authors: Ecem Tiryaki, Saida Ortolano, Gustavo Bodelón, Verónica Salgueiriño
Journal: Advanced Healthcare Materials (2023)

This study compares two kinds of magnetic microbeads with different surface features and cell entry pathways, aiming to provide insights into how to program their cell uptake and intracellular fate. It is found that a rougher surface enhances the cell uptake of the microbeads, regardless of whether they are pulled by a magnetic field gradient or adsorbed by the cell membrane. However, the entry route affects the intracellular localization of the microbeads: The magnetically dragged microbeads reach the cytoplasm, while the adsorbed microbeads stay in the late endosomes and lysosomes. This suggests that different strategies can be used to target different cellular compartments with magnetic microbeads. Moreover, it is demonstrated that the cells containing the microbeads can be moved and regrown at specific locations by applying a magnetic field gradient, showing the potential of these magnetic microbeads for cell delivery and manipulation.
Biomimetic Connection of Transcutaneous Implants with Skin
Authors: Tobias Weigel, Bastian Christ, Sofia Dembski, Andrea Ewald, Dieter Groneberg, Jan Hansmann, Robert Luxenhofer, Marco Metzger, Heike Walles, Christian Willy, Florian Groeber‐Becker, Jörn Probst
Journal: Advanced Healthcare Materials (2023)

Bacterial infection is a crucial complication in implant restoration, in particular in permanent skin-penetrating implants. Therein, the resulting gap between transcutaneous implant and skin represents a permanent infection risk, limiting the field of application and the duration of application. To overcome this limitation, a tight physiological connection is required to achieve a biological and mechanical welding for a long-term stable closure including self-healing probabilities. This study describes a new approach, wherein the implant is connected covalently to a highly porous electrospun fleece featuring physiological dermal integration potential. The integrative potential of the scaffold is shown in vitro and confirmed in vivo, further demonstrating tissue integration by neovascularization, extracellular matrix formation, and prevention of encapsulation. To achieve a covalent connection between fleece and implant surface, self-initiated photografting and photopolymerization of hydroxyethylmethacrylate is combined with a new crosslinker (methacrylic acid coordinated titanium-oxo clusters) on proton-abstractable implant surfaces. For implant modification, the attached fleece is directed perpendicular from the implant surface into the surrounding dermal tissue. First in vitro skin implantations demonstrate the implants' dermal integration capability as well as wound closure potential on top of the fleece by epithelialization, establishing a bacteria-proof and self-healing connection of skin and transcutaneous implant.
Magnetic‐Responsive Carbon Nanotubes Composite Scaffolds for Chondrogenic Tissue Engineering
Authors: Muthusamy Saranya, Aldeliane M. da Silva, Hanna Karjalainen, Geir Klinkenberg, Ruth Schmid, Birgitte McDonagh, Peter P. Molesworth, Margrét S. Sigfúsdóttir, Ane Marit Wågbø, Susana. G. Santos, Cristiana Couto, Ville‐Pauli Karjalainen, Shuvashis Das Gupta, Topias Järvinen, Luisa de Roy, Andreas. M. Seitz, Mikko Finnilä, Simo Saarakkala, Anne Marie Haaparanta, Lauriane Janssen, Gabriela S. Lorite
Journal: Advanced Healthcare Materials (2023)

The demand for engineered scaffolds capable of delivering multiple cues to cells continues to grow as the interplay between cell fate with microenvironmental and external cues is revealed. Emphasis has been given to develop stimuli-responsive scaffolds. These scaffolds are designed to sense an external stimulus triggering a specific response (e.g., change in the microenvironment, release therapeutics, etc.) and then initiate/modulate a desired biofunction. Here, magnetic-responsive carboxylated multi-walled carbon nanotubes (cMWCNTs) are integrated into 3D collagen/polylactic acid (PLA) scaffold via a reproducible filtration-based method. The integrity and biomechanical performance of the collagen/PLA scaffolds are preserved after cMWCNT integration. In vitro safety assessment of cMWCNT/collagen/PLA scaffolds shows neither cytotoxicity effects nor macrophage pro-inflammatory response, supporting further in vitro studies. The cMWCNT/collagen/PLA scaffolds enhance chondrocytes metabolic activity while maintaining high cell viability and extracellular matrix (i.e., type II collagen and aggrecan) production. Comprehensive in vitro study applying static and pulsed magnetic field on seeded scaffolds shows no specific cell response in dependence with the applied field. This result is independent of the presence or absence of cMWCNT into the collagen/PLA scaffolds. Taken together, these findings provide additional evidence of the benefits to exploit the CNTs outstanding properties in the design of stimuli-responsive scaffolds.
Near‐Infrared II Hemicyanine Dye with Large Stokes Shift Designed by TICT Regulation for Boosting Imaging‐Guided Photothermal Therapy
Authors: Liang Zhao, Han Zhu, You‐Yang Duo, Dai‐Wen Pang, Zhi‐Gang Wang, Shu‐Lin Liu
Journal: Advanced Healthcare Materials (2023)

The serious threat that cancer poses to human health highlights the significance of early detection and effective treatment. The integration of fluorescence diagnosis and photothermal therapy in NIR-II has gained attention due to its high sensitivity, fast response, and noninvasiveness. Fluorescence, produced by the radiative relaxation process of electrons in a molecule, and photothermal, generated by the nonradiative relaxation process of electrons in a molecule, are competing photophysical processes. Hence, it is a challenge for the molecule to balance between the properties of fluorescence and photothermal. In this study, a NIR-II hemicyanine with TICT character is designed to obtain molecules with both better fluorescence and photothermal properties, utilizing positively charged pyridine salt and triphenylamine as electron acceptor and donor, respectively, and oxole as the conjugated π-bridge. HCY-995, one of the synthesized compounds, has a quantum yield of 0.09%, photothermal conversion efficiency of 54.90%, and a significant Stoke shift of 232 nm, which makes it appropriate for the integration of photothermal therapy and high-resolution imaging. This study provides new insights into the development of NIR-II molecules with fluorescent and photothermal integrated properties.
Profiling of SARS‐CoV‐2 neutralizing antibody‐associated antigenic peptides signature using proteome microarray
Authors: Mingkun Wu, Jiangfeng Liu, Xinming Wang, Xiaomei Zhang, Te Liang, Lan Chen, Tingxuan Huang, Yanan Li, Chang Zheng, Yehong Yang, Jianwei Wang, Xiaobo Yu, Li Guo, Juntao Yang, Lili Ren
Journal: MedComm (2023)

The profile of antibodies against antigenic epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during neutralizing antibody (NAb) decay has not been clarified. Using a SARS-CoV-2 proteome microarray that contained viral antigenic peptides, we analyzed the characteristics of the humoral response in patients with coronavirus disease 19 (COVID-19) in a longitudinal study. A total of 89 patients were recruited, and 226 plasma samples were serially collected in 2020. In the antigenic peptide microarray, the level of immunoglobulin G (IgG) antibodies against peptides within the S2 subunit (S-82) and a conserved gene region in variants of interest, open reading frame protein 10 (ORF10-3), were closely associated with the presence of SARS-CoV-2 NAbs. In an independent evaluation cohort of 232 plasma samples collected from 116 COVID-19 cases in 2020, S82-IgG titers were higher in NAbs-positive samples (
Zyxin inhibits the epithelial–mesenchymal transition process in gastric cancer by upregulating SIRT1
Authors: Jing Lou, Sha Geng, Wei He, Song‐Bai Liu, Xinghong Shi, Ying Chang, Shiyuan Han, Panting Qian, Hesham M Amin, Yao‐Hua Song, Yangxin Li, Jin Zhou
Journal: MedComm (2023)

Tumor development relies on the stemness of cancer stem cells, which is regulated by environmental cues. Previous studies have shown that zyxin can inhibit the expression of genes for embryonic stem cell status. In the present study, the expression levels of zyxin protein in cancer tissues and adjacent noncancerous tissues from 73 gastric cancer patients with different clinical stages were analyzed by Western blot. We showed that the relative expression levels of zyxin in gastric cancer tissues (cancer tissues/adjacent tissues) were significantly downregulated in advanced clinical stages. Overexpression of zyxin inhibited the stemness and epithelial-mesenchymal transition (EMT) processes in gastric cancer cells. Zyxin also inhibited the proliferation, migration, and invasion but increased the sensitivity of cancer cells to drugs. Overexpression of zyxin in MKN45 cells inhibited tumor growth in nude mice. We show that the interactions between zyxin and SIRT1 led to the upregulation of SIRT1, reduced acetylation levels of histone H3 K9 and K23, decreased transcription levels of SNAI 1/2, and inhibition of the EMT process. This study demonstrated that zyxin negatively regulates the progression of gastric cancer by inhibiting the stemness of cancer stem cells and EMT. Our findings shed new light on the pathogenesis of gastric cancer.
Metal nanoparticles for cancer therapy: Precision targeting of DNA damage
Authors: Qian Chen, Chunyan Fang, Fan Xia, Qiyue Wang, Fangyuan Li, Daishun Ling
Journal: Acta Pharmaceutica Sinica B (2023)

Cancer, a complex and heterogeneous disease, arises from genomic instability. Currently, DNA damage-based cancer treatments, including radiotherapy and chemotherapy, are employed in clinical practice. However, the efficacy and safety of these therapies are constrained by various factors, limiting their ability to meet current clinical demands. Metal nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer therapy. Their customizable physicochemical properties enable the development of targeted and personalized treatment platforms. In this review, we delve into the design principles and optimization strategies of metal nanoparticles. We shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal nanoparticles. These encompass targeted drug delivery, inhibition of DNA repair mechanisms, induction of cell death, and the cascading immune response. Moreover, we explore the pivotal role of physicochemical factors such as nanoparticle size, stimuli-responsiveness, and surface modification in shaping metal nanoparticle platforms. Finally, we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy, paving the way for novel treatment paradigms.
Surgical Management of Full-Thickness Macular Holes in Macular Telangiectasia Type 2
Authors: Jong G. Park, Sean D. Adrean, Tedi Begaj, Antonio Capone, Steve Charles, San-Ni Chen, Hung-Da Chou, Michael N. Cohen, Stephanie Trejo Corona, Lisa J. Faia, Sunir J. Garg, Bruce R. Garretson, Ninel Z. Gregori, Julia A. Haller, Odette Margit Houghton, Jason Hsu, Jaehyuck Jo, Richard S. Kaiser, Chi-Chun Lai, Mohamed Moghazy Mahgoub, Mahsaw Mansoor, Ryo Matoba, Yuki Morizane, Marcio B. Nehemy, Paul V. Raphaelian, Carl D. Regillo, Alan J. Ruby, Margaret M. Runner, Scott R. Sneed, Elliott H. Sohn, Marc J. Spirn, James F. Vander, Taku Wakabayashi, Jeremy D. Wolfe, Charles C. Wykoff, Yoshihiro Yonekawa, Young Hee Yoon, Tamer H. Mahmoud
Journal: Ophthalmology (2023)
Antibody responses to recombinant vesicular stomatitis virus-Zaire Ebolavirus vaccination for Ebola virus disease across doses and continents: 5-year durability
Authors: Angela Huttner, Selidji Todagbe Agnandji, Olivier Engler, Jay W. Hooper, Steve Kwilas, Keersten Ricks, Tamara L. Clements, Hulda R. Jonsdottir, Sravya Sowdamini Nakka, Sylvia Rothenberger, Peter Kremsner, Roland Züst, Donata Medaglini, Tom Ottenhoff, Ali M. Harandi, Claire-Anne Siegrist, Selidji Todagbe Agnandji, Sanjeev Krishna, Peter G. Kremsner, Jessica S. Brosnahan, Marylyn M. Addo, Stephan Becker, Verena Kra¨hling, Philip Bejon, Patricia Njuguna, Claire-Anne Siegrist, Angela Huttner, Marie-Paule Kieny, Vasee Moorthy, Patricia Fast, Barbara Savarese, Olivier Lapujade, Selidji Todagbe Agnandji, Rafi Ahmed, Jenna Anderson, Floriane Auderset, Philip Bejon, Luisa Borgianni, Jessica Brosnahan, Annalisa Ciabattini, Olivier Engler, Marie¨lle C. Haks, Ali Harandi, Donald Gray Heppner, Alice Gerlini, Angela Huttner, Peter Gottfried Kremsner, Donata Medaglini, Thomas Monath, Francis Ndungu, Patricia Njuguna, Tom HM. Ottenhoff, David Pejoski, Mark Page, Gianni Pozzi, Francesco Santoro, Claire-Anne Siegrist, Selidji Todagbe Agnandji, Floriane Auderset, Luisa Borgianni, Sheri Dubey, Olivier Engler, José F. Fernandes, Marie¨lle C. Haks, Ali Harandi, Alice Gerlini, Angela Huttner, Peter Gottfried Kremsner, Simone Lucchesi, Donata Medaglini, Thomas Monath, Helder Nakaya, Sravya S. Nakka, Fiona Orourke, Tom HM. Ottenhoff, David Pejoski, Gianni Pozzi, Sylvia Rothenberger, Francesco Santoro, Suzanne van Veen, Eleonora Vianello, Claire-Anne Siegrist
Journal: Clinical Microbiology and Infection (2023)
Plant-derived nanovesicles as an emerging platform for cancer therapy
Authors: Hanzhe Liu, Guo-Feng Luo, Zhengjun Shang
Journal: Acta Pharmaceutica Sinica B (2023)

Plant-derived nanovesicles (PDNVs) derived from natural green products have emerged as an attractive nanoplatform in biomedical application. They are usually characterized by unique structural and biological functions, such as the bioactive lipids/proteins/nucleic acids as therapeutics and targeting groups, immune-modulation, and long-term circulation. With the rapid development of nanotechnology, materials, and synthetic chemistry, PDNVs can be engineered with multiple functions for efficient drug delivery and specific killing of diseased cells, which represent an innovative biomaterial with high biocompatibility for fighting against cancer. In this review, we provide an overview of the state-of-the-art studies concerning the development of PDNVs for cancer therapy. The original sources, methods for obtaining PDNVs, composition and structure are introduced systematically. With an emphasis on the featured application, the inherent anticancer properties of PDNVs as well as the strategies in constructing multifunctional PDNVs-based nanomaterials will be discussed in detail. Finally, some scientific issues and technical challenges of PDNVs as promising options in improving anticancer therapy will be discussed, which are expected to promote the further development of PDNVs in clinical translation.
Nasal mucosal IgA levels against SARS-CoV-2 and seasonal coronaviruses are low in children but boosted by reinfection
Authors: Alexander C. Dowell, Gokhan Tut, Jusnara Begum, Rachel Bruton, Christopher Bentley, Megan Butler, Grace Uwenedi, Jianmin Zuo, Annabel A. Powell, Andrew J. Brent, Bernadette Brent, Frances Baawuah, Ifeanyichukwu Okike, Joanne Beckmann, Shazaad Ahmad, Felicity Aiano, Joanna Garstang, Mary E. Ramsay, Paul Moss, Shamez N. Ladhani
Journal: Journal of Infection (2023)

Repeated coronavirus infections in childhood drive progressive maturation of systemic immune responses into adulthood. Analyses of immune responses in children have focused primarily upon systemic assessment but the importance of mucosal immunity is increasingly recognised. We studied virus-specific antibody responses in contemporaneous nasal swabs and blood samples from 99 children (4-15 years) and 28 adults (22-56 years), all of whom had prior SARS-CoV-2 infection. Whilst mucosal IgA titres against Influenza and Respiratory Syncytial virus were comparable between children and adults, those against all coronaviruses, including SARS-CoV-2, were lower in children. Mucosal IgA antibodies demonstrated comparable relative neutralisation capacity in both groups and retained activity against recent omicron variants such as XBB.1 which are highly evasive of IgG neutralisation. SARS-CoV-2 reinfection preferentially enhanced mucosal IgA responses whilst the impact of vaccination was more modest. Nasal IgA levels against coronaviruses thus display a pattern of incremental response to reinfection which likely determines the natural history of reinfection. This highlights the particular significance of developing mucosal vaccines against coronaviruses in children.
Breakthroughs in understanding and treating eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERs Symposium at the 2022 American Academy of Allergy, Asthma &amp; Immunology Meeting
Authors: Mirna Chehade, Benjamin L. Wright, Dan Atkins, Seema S. Aceves, Steven J. Ackerman, Amal H. Assa’ad, Maureen Bauer, Margaret H. Collins, Scott P. Commins, Carla M. Davis, Evan S. Dellon, Bethan Doerfler, Gerald J. Gleich, Sandeep K. Gupta, David A. Hill, Elizabeth T. Jensen, David Katzka, Kara Kliewer, Ellyn Kodroff, Leah C. Kottyan, Shay Kyle, Amanda B. Muir, Robert D. Pesek, Kathryn Peterson, Wayne G. Shreffler, Jonathan M. Spergel, Mary Jo Strobel, Joshua Wechsler, Nives Zimmermann, Glenn T. Furuta, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2023)
ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment
Authors: Santiago Ponce, Susana Cedrés, Charles Ricordel, Nicolas Isambert, Santiago Viteri, Mercedes Herrera-Juarez, Alex Martinez-Marti, Alejandro Navarro, Mathieu Lederlin, Xavier Serres, Jon Zugazagoitia, Sylvia Vetrhus, Magnus Jaderberg, Thomas Birkballe Hansen, Victor Levitsky, Luis Paz-Ares
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background ONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to an immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcomes. Methods In this open-label, randomized study, patients with unresectable MPM received intratumoral ONCOS-102 (3×10 11 virus particles on days 1, 4, 8, 36, 78, and 120) and pemetrexed plus cisplatin/carboplatin (from day 22), or pemetrexed plus cisplatin/carboplatin alone. The primary endpoint was safety. Overall survival (OS), progression-free survival, objective response rate, and tumor immunologic activation (baseline and day 36 biopsies) were also assessed. Results In total, 31 patients (safety lead-in: n=6, randomized: n=25) were enrolled. Anemia (15.0% and 27.3%) and neutropenia (40.0% and 45.5%) were the most frequent grade ≥3 adverse events (AEs) in the ONCOS-102 (n=20) and chemotherapy-alone (n=11) cohorts. No patients discontinued ONCOS-102 due to AEs. No statistically significant difference in efficacy endpoints was observed. There was a numerical improvement in OS (30-month OS rate 34.1% vs 0; median OS 20.3 vs 13.5 months) with ONCOS-102 versus chemotherapy alone in chemotherapy-naïve patients (n=17). By day 36, ONCOS-102 was associated with increased T-cell infiltration and immune-related gene expression that was not observed in the control cohort. Substantial immune activation in the tumor microenvironment was associated with survival at month 18 in the ONCOS-102 cohort. Conclusions ONCOS-102 plus pemetrexed and cisplatin/carboplatin was well tolerated by patients with MPM. In injected tumors, ONCOS-102 promoted a proinflammatory environment, including T-cell infiltration, which showed association with survival at month 18.
Climate change and respiratory health: a European Respiratory Society position statement
Authors: Ana Maria Vicedo-Cabrera, Erik Melén, Francesco Forastiere, Ulrike Gehring, Klea Katsouyanni, Arzu Yorgancioglu, Charlotte Suppli Ulrik, Kjeld Hansen, Pippa Powell, Brian Ward, Barbara Hoffmann, Zorana Jovanovic Andersen
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Climate change is a major threat to lung patients, causing more frequent and extreme weather events, prolonged aeroallergen seasons, and poorer air quality. ERS calls on the health community and policymakers to act now and prepare for a complex future.</b>https://bit.ly/3pO27Ne
Knockdown of PGC1α suppresses dysplastic oral keratinocytes proliferation through reprogramming energy metabolism
Authors: Yunkun Liu, Nengwen Huang, Xianghe Qiao, Zhiyu Gu, Yongzhi Wu, Jinjin Li, Chengzhou Wu, Bo Li, Longjiang Li
Journal: International Journal of Oral Science (2023)

Oral potentially malignant disorders (OPMDs) are precursors of oral squamous cell carcinoma (OSCC). Deregulated cellular energy metabolism is a critical hallmark of cancer cells. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) plays vital role in mitochondrial energy metabolism. However, the molecular mechanism of PGC1α on OPMDs progression is less unclear. Therefore, we investigated the effects of knockdown PGC1α on human dysplastic oral keratinocytes (DOKs) comprehensively, including cell proliferation, cell cycle, apoptosis, xenograft tumor, mitochondrial DNA (mtDNA), mitochondrial electron transport chain complexes (ETC), reactive oxygen species (ROS), oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake. We found that knockdown PGC1α significantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo, induced S-phase arrest, and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis. Mechanistically, downregulated of PGC1α decreased mtDNA, ETC, and OCR, while enhancing ROS, glucose uptake, ECAR, and glycolysis by regulating lactate dehydrogenase A (LDHA). Moreover, SR18292 (an inhibitor of PGC1α) induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression. Thus, our work suggests that PGC1α plays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism, acting as a potential therapeutic target for OPMDs.